Method for producing polygylcerol esters of polycarboxylic acids esterified with oxobutanol

Abstract

The invention relates to a method for producing polyglycerol esters of polycarboxylic acids esterified with oxobutanol, especially mono- or polyvalent polyglycerol esters of polycarboxylic acids esterified with 4-oxo-4-(C 1 -C 5 -alkoxy)-2-butanol or with 4-oxo-4-(hydroxy-C 3 -C 5 -alkoxy)-2-butanol, as well as the products thus obtained and their use.

1 - 81 . (canceled) 
     
     
         82 . A method for producing polyglycerol esters of polycarboxylic acids esterified with oxobutanol,
 wherein the following reactants (i), (ii) and (iii) are reacted with one another:
 (i) at least one oxobutanol of the general formula (I)
   CH 3 —CH(OH)—CH 2 —C(O)OR 1   (I)
 
 wherein, in the general formula (I), the radical R 1  is selected among C 1 -C 5 -alkyl and hydroxy-C 3 -C 5 -alkyl, 
 
 (ii) at least one polycarboxylic acid (II) selected among the polycarboxylic acid (II) in its free form and in the form of its salts, esters and anhydrides, 
 (iii) at least one polyglycerol (III); 
   wherein the method is carried out as one of a one-step method and a method comprising several steps, and   wherein the method is carried out in the absence of any solvent;   wherein, when the polycarboxylic acid (II) is used in the form of a free acid, water is formed simultaneously during the reaction, wherein the water is continuously withdrawn from the reaction;   wherein, when the polycarboxylic acid (II) is used in the form of an anhydride, the corresponding free polycarboxylic acid (II) and water are formed, wherein the resulting free polycarboxylic acid (II) is further reacted or, after the reaction has taken place, is removed and recycled and wherein the water is continuously withdrawn from the reaction;   wherein, when the polycarboxylic acid (II) is used in the form of an ester, the corresponding ester alcohol and water are formed, wherein the resulting ester alcohol and water are continuously withdrawn from the reaction;   so that, as a reaction product (IV), one or more polyglycerol esters of polycarboxylic acids esterified with oxobutanol are obtained.   
     
     
         83 . The method according to  claim 82 ,
 wherein the method is carried out in at least two steps,   wherein:
 (a) in a first method step (a), the at least one oxobutanol of the general formula (I) is reacted with the at least one polycarboxylic acid (II) in an esterification reaction,
 so that, as a reaction intermediate (IV′) of method step (a), one or more polycarboxylic acid esters of oxobutanol are obtained; and 
 
 (b) subsequently, in a second method step (b), the reaction intermediate product (IV′) obtained in method step (a) is reacted with the at least one polyglycerol (III) in an esterification reaction. 
   
     
     
         84 . The method according to  claim 82 ,
 wherein the polycarboxylic acid (II) is selected from the group consisting of succinic acid, tartaric acid, citric acid, malic acid, adipic acid, fumaric acid and maleic acid.   
     
     
         85 . The method according to  claim 82 ,
 wherein the polycarboxylic acid (II) is selected among naturally occurring carboxylic acids and their anhydrides and derivatives occurring in one of human and animal metabolism.   
     
     
         86 . The method according to  claim 82 ,
 wherein the polycarboxylic acid (II) is an ingredient approved under food law.   
     
     
         87 . The method according to  claim 82 ,
 wherein the polyglycerol corresponds to the general formula (IIIa)
   HO—CH 2 —CH(OH)—CH 2 —[O—CH 2 —CH(OH)—CH 2 ] p —OH  (IIIa)
 
   wherein, in general formula (IIIa), the variable p represents an integer from 1 to 6.   
     
     
         88 . The method according to  claim 82 ,
 wherein the polyglycerol (III) is a diglycerol of formula (IIIb)
   HO—CH 2 —CH(OH)—CH 2 —O—CH 2 —CH(OH)—CH 2 —OH  (IIIb).
 
   
     
     
         89 . The method according to  claim 82 ,
 wherein the polyglycerol (III) is not propane-1,2,3-triol (glycerol).   
     
     
         90 . The method according to  claim 82 ,
 wherein hydroxyl groups and carboxyl groups still present in the reaction product after the reaction has been performed are at least partially functionalized.   
     
     
         91 . The method according to  claim 82 ,
 wherein the reaction is followed by an at least partial esterification of hydroxyl groups and carboxyl groups still present after the reaction has been performed.   
     
     
         92 . A reaction intermediate product in the form of a polycarboxylic acid ester of oxobutanol,
 wherein the reaction intermediate product is obtainable as the reaction intermediate product (IV′) of the first method step (a) of the method according to  claim 83 .   
     
     
         93 . A reaction product in the form of a polyglycerol ester of polycarboxylic acids esterified with oxobutanol,
 wherein the reaction product is obtainable by the method according to  claim 82 .   
     
     
         94 . A polyglycerol ester of polycarboxylic acids esterified with oxobutanol,
 wherein the polyglycerol ester of polycarboxylic acids esterified with oxobutanol corresponds to the general formula (IVa)
   R 4 O—CH 2 —CH(OR 4 )—CH 2 —[O—CH 2 —CH(OR 4 )—CH 2 ] p —OR 4   (IVa)
 
   wherein, in the general formula (IVa), the radical R 4 , independently of one another, represents:
 hydrogen; 
 a radical R 1 —O—C(O)—CH 2 —CH(CH 3 )—O—(O)C—X—C(O)—,
 wherein the radical R 1  is selected among C 1 -C 5 -alkyl and hydroxy-C 3 -C 5 -alkyl, and 
 wherein X represents a saturated or unsaturated organic radical comprising 1 to 10 carbon atoms, which may be mono- or polysubstituted with one or more of the following radicals: hydroxyl, carboxyl, —O—C(O)—CH 2 —CH(OH)—CH 3  and —C(O)—O—CH(CH 3 )—CH 2 —C(O)OR 1  with R 1  as defined hereinbefore; 
 a radical H 3 C—CH(OH)—CH 2 —C(O)—; 
 a radical HOOC—X—C(O)— with X as defined hereinbefore; 
 
   however, with the proviso that at least one radical R 4  represents a radical R 1 —O—C(O)—CH 2 —CH(CH 3 )—O—(O)C—X—C(O)— as defined hereinbefore; and   wherein, in the general formula (IVa), the variable p represents an integer from 1 to 6.   
     
     
         95 . The polyglycerol ester of polycarboxylic acids esterified with oxobutanol according to  claim 94 ,
 wherein the polyglycerol ester of polycarboxylic acids esterified with oxobutanol corresponds to the general formula (IVa)
   R 4 O—CH 2 —CH(OR 4 )—CH 2 —[O—CH 2 —CH(OR 4 )—CH 2 ] p —OR 4   (IVa)
 
   wherein, in the general formula (IVa), the radical R*, independently of one another, represents:
 hydrogen; 
 a radical R 1 —O—C(O)—CH 2 —CH(CH 3 )—O—(O)C—X—C(O)—,
 wherein the radical R 1  is selected among C 1 -C 5 -alkyl and hydroxy-C 3 -C 5 -alkyl, and 
 wherein X represents a saturated or unsaturated organic radical comprising 1 to 10 carbon atoms, which may be mono- or polysubstituted with one or more of the following radicals: hydroxyl, carboxyl, —O—C(O)—CH 2 —CH(OH)—CH 3  and —C(O)—O—CH(CH 3 )—CH 2 —C(O)OR 1  with R 1  as defined hereinbefore; 
 
   however, with the proviso that at least one radical R 1  represents a radical R 1 —O—C(O)—CH 2 —CH(CH 3 )—O—(O)C—X—C(O)— as defined hereinbefore; and   wherein, in the general formula (IVa), the variable p represents an integer from 1 to 6.   
     
     
         96 . The polyglycerol ester of polycarboxylic acids esterified with oxobutanol according to  claim 94 ,
 wherein the polyglycerol ester of polycarboxylic acids esterified with oxobutanol corresponds to the general formula (IVa)
   R 1 O—CH 2 —CH(OR 4 )—CH 2 —[O—CH 2 —CH(OR 4 )—CH 2 ] p —OR 4   (IVa)
 
   wherein, in the general formula (IVa), the radical R 4 , independently of one another, represents:
 hydrogen; 
 a radical R 1 —O—C(O)—CH 2 —CH(CH 3 )—O—(O)C—X—C(O)—,
 wherein the radical R 1  is selected among C 1 -C 5 -alkyl and hydroxy-C 3 -C 5 -alkyl, and 
 wherein X represents a saturated or unsaturated organic radical comprising 1 to 10 carbon atoms, which is mono- or polysubstituted with one or more of the following radicals: hydroxyl, carboxyl, —O—C(O)—CH 2 —CH(OH)—CH 3  and —C(O)—O—CH(CH 3 )—CH 2 —C(O)OR 1  with R 1  as defined hereinbefore; 
 
   however, with the proviso that at least one radical R 1  represents a radical R 1 —O—C(O)—CH 2 —CH(CH 3 )—O—(O)C—X—C(O)—, as defined hereinbefore; and   wherein, in the general formula (IVa), the variable p represents an integer from 1 to 6.   
     
     
         97 . The polyglycerol ester of polycarboxylic acids esterified with oxobutanol according to  claim 94 ,
 wherein the polyglycerol ester of polycarboxylic acids esterified with oxobutanol corresponds to the general formula (IVb)
   R 5 O—CH 2 —CH(OR 5 )—CH 2 —[O—CH 2 —CH(OR 5 )—CH 2 ] p —OR 5   (IVb)
 
   wherein, in the general formula (IVb), the radical R 5 , independently of one another, represents:
 hydrogen; 
 a radical R 1 —O—C(O)—CH 2 —CH(CH 3 )—O—Y—,
 wherein the radical R 1  is selected among C 1 -C 5 -alkyl and hydroxy-C 3 -C 5 -alkyl, and 
 wherein Y is derived from a polycarboxylic acid selected from the group consisting of succinic acid, tartaric acid, citric acid, malic acid, adipic acid, fumaric acid and maleic acid, especially wherein in the case of citric acid the further carboxyl group present is esterified with a radical —CH(CH 3 )—CH 2 —C(O)OR 1  with R 1  as defined hereinbefore, 
 
 a radical H 3 C—CH(OH)—CH 2 —C(O)—; 
 a radical —Y—OH with Y as defined hereinbefore; 
   however, with the proviso that at least one radical R 5  represents a radical R 1 —O—C(O)—CH 2 —CH(CH 3 )—O—Y— with R 1  and Y each as defined hereinbefore; and   wherein, in the general formula (IVb), the variable p represents an integer from 1 to 6.   
     
     
         98 . The polyglycerol ester of polycarboxylic acids esterified with oxobutanol according to  claim 94 ,
 wherein the polyglycerol ester of polycarboxylic acids esterified with oxobutanol corresponds to the general formula (IVb)
   R 5 O—CH 2 —CH(OR 5 )—CH 2 —[O—CH 2 —CH(OR 5 )—CH 2 ] p —OR 5   (IVb)
 
   wherein, in the general formula (IVb), the radical R 5 , independently of one another, represents:
 hydrogen; 
 a radical R 1 —O—C(O)—CH 2 —CH(CH 3 )—O—Y—,
 wherein the radical R 1  is selected among C 1 -C 5 -alkyl and hydroxy-C 3 -C 5 -alkyl, and 
 wherein Y represents one of the following radicals: 
 
   
       
         
           
           
               
               
           
         
         
           
             wherein, in the radicals, the radical R 3  is selected among hydrogen and a radical —CH(CH 3 )—CH 2 —C(O)OR 1  with R 1  as defined hereinbefore; 
           
           a radical H 3 C—CH(OH)—CH 2 —C(O)—; 
           a radical Y—OH with Y as defined hereinbefore; 
         
         however, with the proviso that at least one radical R 5  represents a radical R 1 —O—C(O)—CH 2 —CH(CH 3 )—O—Y— with R 1  and Y each as defined hereinbefore; and 
         wherein, in the general formula (IVb), the variable p represents an integer from 1 to 6. 
       
     
     
         99 . The polyglycerol ester of polycarboxylic acids esterified with oxobutanol according to  claim 94 ,
 wherein the polyglycerol ester of polycarboxylic acids esterified with oxobutanol corresponds to the general formula (IVc)
   R 4 O—CH 2 —CH(OR 4 )—CH 2 —O—CH 2 —CH(OR 4 )—CH 2 —OR 4   (IVc)
 
   wherein, in the general formula (IVc), the radical R 4 , independently of one another, represents
 hydrogen; 
 a radical R 1 —O—C(O)—CH 2 —CH(CH 3 )—O—(O)C—X—C(O)—,
 wherein the radical R 1  is selected among C 1 -C 5 -alkyl and hydroxy-C 3 -C 5 -alkyl, and 
 wherein X represents a saturated or unsaturated organic radical comprising 1 to 10 carbon atoms, which may be mono- or polysubstituted with one or more of the following radicals: hydroxyl, carboxyl, —O—C(O)—CH 2 —CH(OH)—CH 3  and —C(O)—O—CH(CH 3 )—CH 2 —C(O)OR 1  with R 1  as defined hereinbefore; 
 
 a radical H 3 C—CH(OH)—CH 2 —C(O)—; 
 a radical HOOC—X—C(O)— with X as defined hereinbefore; 
   however, with the proviso that at least one radical R 1  represents a radical R 1 —O—C(O)—CH 2 —CH(CH 3 )—O—(O)C—X—C(O)— as defined hereinbefore.   
     
     
         100 . The polyglycerol ester of polycarboxylic acids esterified with oxobutanol according to  claim 94 ,
 wherein the polyglycerol ester of polycarboxylic acids esterified with oxobutanol corresponds to the general formula (IVd)
   R 5 O—CH 2 —CH(OR 5 )—CH 2 —O—CH 2 —CH(OR 5 )—CH 2 —OR 5   (IVd)
 
   wherein, in the general formula (IVd), the radical R 5 , independently of one another, represents
 hydrogen; 
 a radical R 1 —O—C(O)—CH 2 —CH(CH 3 )—O—Y—,
 wherein the radical R 1  is selected among C 1 -C 5 -alkyl and hydroxy-C 3 -C 5 -alkyl, and 
 wherein Y represents one of the following radicals: 
 
   
       
         
           
           
               
               
           
         
         
           
             wherein, in the radicals, the radical R 3  represents hydrogen or a radical —CH(CH 3 )—CH 2 —C(O)OR 1  with R 1  as defined hereinbefore; 
           
           a radical H 3 C—CH(OH)—CH 2 —C(O)—; 
           a radical Y—OH with Y as defined hereinbefore; 
         
         however, with the proviso that at least one radical R 5  represents a radical R 1 —O—C(O)—CH 2 —CH(CH 3 )—O—Y— with R 1  and Y each as defined hereinbefore. 
       
     
     
         101 . A mixture comprising at least two different polyglycerol esters of polycarboxylic acids esterified with oxobutanol, as defined in  claim 94 . 
     
     
         102 . A pharmaceutical composition comprising at least one polyglycerol ester of polycarboxylic acids esterified with oxobutanol,
 wherein the polyglycerol ester of polycarboxylic acids esterified with oxobutanol corresponds to the general formula (IVa)
   R 4 O—CH 2 —CH(OR 4 )—CH 2 —[O—CH 2 —CH(OR 4 )—CH 2 ] p —OR 4   (IVa)
 
   wherein, in the general formula (IVa), the radical R 4 , independently of one another, represents:
 hydrogen; 
 a radical R 1 —O—C(O)—CH 2 —CH(CH 3 )—O—(O)C—X—C(O)—,
 wherein the radical R 1  is selected among C 1 -C 5 -alkyl and hydroxy-C 3 -C 5 -alkyl, and 
 wherein X represents a saturated or unsaturated organic radical comprising 1 to 10 carbon atoms, which may be mono- or polysubstituted with one or more of the following radicals: hydroxyl, carboxyl, —O—C(O)—CH 2 —CH(OH)—CH 3  and —C(O)—O—CH(CH 3 )—CH 2 —C(O)OR 1  with R 1  as defined hereinbefore; 
 
 a radical H 3 C—CH(OH)—CH 2 —C(O)—; 
 a radical HOOC—X—C(O)— with X as defined hereinbefore; 
   however, with the proviso that at least one radical R 4  represents a radical R 1 —O—C(O)—CH 2 —CH(CH 3 )—O—(O)C—X—C(O)— as defined hereinbefore; and   wherein, in the general formula (IVa), the variable p represents an integer from 1 to 6.   
     
     
         103 . The pharmaceutical composition according to  claim 102 ,
 wherein the pharmaceutical composition is a drug or a medicament.   
     
     
         104 . A method of treating a human or an animal suffering from a disease of the human or animal body,
 wherein the method comprises the step of administering to said human or animal a therapeutically efficient amount of at least one polyglycerol ester of polycarboxylic acids esterified with oxobutanol,   wherein the polyglycerol ester of polycarboxylic acids esterified with oxobutanol corresponds to the general formula (IVa)
   R 4 O—CH 2 —CH(OR 4 )—CH 2 —[O—CH 2 —CH(OR 4 )—CH 2 ] p —OR 4   (IVa)
 
   wherein, in the general formula (IVa), the radical R*, independently of one another, represents:
 hydrogen; 
 a radical R 1 —O—C(O)—CH 2 —CH(CH 3 )—O—(O)C—X—C(O)—,
 wherein the radical R 1  is selected among C 1 -C 5 -alkyl and hydroxy-C 3 -C 5 -alkyl, and 
 wherein X represents a saturated or unsaturated organic radical comprising 1 to 10 carbon atoms, which may be mono- or polysubstituted with one or more of the following radicals: hydroxyl, carboxyl, —O—C(O)—CH 2 —CH(OH)—CH 3  and —C(O)—O—CH(CH 3 )—CH 2 —C(O)OR 1  with R 1  as defined hereinbefore; 
 
 a radical H 3 C—CH(OH)—CH 2 —C(O)—; 
 a radical HOOC—X—C(O)— with X as defined hereinbefore; 
   however, with the proviso that at least one radical R 4  represents a radical R 1 —O—C(O)—CH 2 —CH(CH 3 )—O—(O)C—X—C(O)— as defined hereinbefore; and   wherein, in the general formula (IVa), the variable p represents an integer from 1 to 6.   
     
     
         105 . The method according to  claim 104 ,
 wherein the disease is selected among diseases associated with a disorder of human or animal energy metabolism.   
     
     
         106 . The method according to  claim 104 ,
 wherein the disease is selected among diseases associated with a disorder of human or animal keto-body metabolism.   
     
     
         107 . A food product comprising at least one polyglycerol ester of polycarboxylic acids esterified with oxobutanol,
 wherein the polyglycerol ester of polycarboxylic acids esterified with oxobutanol corresponds to the general formula (IVa)
   R 4 O—CH 2 —CH(OR 4 )—CH 2 —[O—CH 2 —CH(OR 4 )—CH 2 ] p —OR 4   (IVa)
 
   wherein, in the general formula (IVa), the radical R 4 , independently of one another, represents:
 hydrogen; 
 a radical R 1 —O—C(O)—CH 2 —CH(CH 3 )—O—(O)C—X—C(O)—,
 wherein the radical R 1  is selected among C 1 -C 5 -alkyl and hydroxy-C 3 -C 5 -alkyl, and 
 wherein X represents a saturated or unsaturated organic radical comprising 1 to 10 carbon atoms, which may be mono- or polysubstituted with one or more of the following radicals: hydroxyl, carboxyl, —O—C(O)—CH 2 —CH(OH)—CH 3  and —C(O)—O—CH(CH 3 )—CH 2 —C(O)OR 1  with R 1  as defined hereinbefore; 
 
 a radical H 3 C—CH(OH)—CH 2 —C(O)—; 
 a radical HOOC—X—C(O)— with X as defined hereinbefore; 
   however, with the proviso that at least one radical R 4  represents a radical R 1 —O—C(O)—CH 2 —CH(CH 3 )—O—(O)C—X—C(O)— as defined hereinbefore; and   wherein, in the general formula (IVa), the variable p represents an integer from 1 to 6.   
     
     
         108 . The food product according to  claim 107 ,
 wherein the food product is selected from the group consisting of a food, a dietary supplement, a functional food, a novel food, a food additive, a food supplement, a dietary food, a power snack, an appetite suppressant and a strength sports supplement and an endurance sports supplement.